Several publications and patent documents are cited throughout the specification in order to describe the state of the art to which this invention pertains. Each of these citations is incorporated herein by reference as though set forth in full.
Many bacterial diseases have become more deadly as bacteria have developed resistance to treatment with antibiotics. About half of all antibiotics target bacterial protein synthesis, but there are no inhibitors currently in use in clinical practice that target ternary complex formation (aminoacyl-tRNA, EF-Tu, and GTP). There are a few known naturally occurring inhibitors of this step that work in vitro (e.g., kirromycin and others), but these are not effective against gram-negative bacteria because they do not enter bacterial cells. Accordingly, there is a strong need to identify compounds for use as new antibiotics, including those which target the ternary complex.